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Children with an anxious temperament (AT) are at risk for developing psychiatric disorders along the internalizing spectrum, including anxiety and depression. Like these disorders, AT is a multidimensional phenotype and children with extreme anxiety show varying mixtures of physiological, behavioral, and other symptoms. Using a well-validated juvenile monkey model of AT, we addressed the degree to which this phenotypic heterogeneity reflects fundamental differences or similarities in the underlying neurobiology. The rhesus macaque is optimal for studying AT because children and young monkeys express the anxious phenotype in similar ways and have similar neurobiology. Fluorodeoxyglucose (FDG)-positron emission tomography (FDG-PET) in 238 freely behaving monkeys identified brain regions where metabolism predicted variation in three dimensions of the AT phenotype: hypothalamic-pituitary-adrenal (HPA) activity, freezing behavior, and expressive vocalizations. We distinguished brain regions that predicted all three dimensions of the phenotype from those that selectively predicted a single dimension. Elevated activity in the central nucleus of the amygdala and the anterior hippocampus was consistently found across individuals with different presentations of AT. In contrast, elevated activity in the lateral anterior hippocampus was selective to individuals with high levels of HPA activity, and decreased activity in the motor cortex (M1) was selective to those with high levels of freezing behavior. Furthermore, activity in these phenotype-selective regions mediated relations between amygdala metabolism and different expressions of anxiety. These findings provide a framework for understanding the mechanisms that lead to heterogeneity in the clinical presentation of internalizing disorders and set the stage for developing improved interventions.
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In children, behavioral inhibition (BI) in response to potential threat predicts the development of anxiety and affective disorders, and primate lesion studies suggest involvement of the orbitofrontal cortex (OFC) in mediating BI. Lesion studies are essential for establishing causality in brain-behavior relationships, but should be interpreted cautiously because the impact of a discrete lesion on a complex neural circuit extends beyond the lesion location. Complementary functional imaging methods assessing how lesions influence other parts of the circuit can aid in precisely understanding how lesions affect behavior. Using this combination of approaches in monkeys, we found that OFC lesions concomitantly alter BI and metabolism in the bed nucleus of stria terminalis (BNST) region and that individual differences in BNST activity predict BI. Thus it appears that an important function of the OFC in response to threat is to modulate the BNST, which may more directly influence the expression of BI.
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Davidson and Schwartz (1) have proposed a psychobiological analysis of anxiety that emphasizes the patterning of multiple processes in the generation and self-regulation of this state. The present article specifically reviews recent research on cognitive and somatic components of anxiety. A dual component scale which separately assesses cognitive and somatic trait anxiety is described and applied to the study of the differential effects of a somatic (physical exercise) and a cognitive (meditation) relaxation procedure. A total of 77 subjects was employed; 44 regularly practiced physical exercise and 33 regularly practiced meditation for comparable periods of time. As predicted, subjects practicing physical exercise reported relatively less somatic and more cognitive anxiety than meditators. These data suggest that specific subcomponents of anxiety may be differentially associated with relaxation techniques engaging primarily cognitive versus somatic subsystems. It is proposed that relaxation consists of (1) a generalized reduction to multiple physiological systems (termed the relaxation response by Benson) and (2) a more specific pattern of changes superimposed upon this general reduction, which is elicited by the particular techniques employed. The data from this retrospective study need to be followed up by prospective studies to establish the precise mechanisms for these effects.
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Children with a cancer diagnosis experience symptom distress, including anxiety, because of the disease and its treatment. Parents experience stress and anxiety because of the uncertainty of the disease as well as the suffering of their children. Yoga is a complementary intervention that has physiological and psychological benefits in healthy children and healthy and chronically ill adults. On an inpatient hematology/oncology unit, 11 children aged 6 to 12 years, 5 adolescents aged 13 to 18 years, and 33 parents participated in a single yoga session tailored to the needs and abilities of the patients and parents. Sense of well-being pre- and postclass was measured with the Spielberger State Anxiety Scale. Children had normal anxiety scores preclass that did not change. Adolescents and parents experienced significant decreases in anxiety scores, and all cohorts gave positive feedback about the experience. The authors conclude that yoga is a feasible intervention for this population and is beneficial to adolescents and parents.
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Individuals with fragile X syndrome (FXS) commonly display characteristics of social anxiety, including gaze aversion, increased time to initiate social interaction, and difficulty forming meaningful peer relationships. While neural correlates of face processing, an important component of social interaction, are altered in FXS, studies have not examined whether social anxiety in this population is related to higher cognitive processes, such as memory. This study aimed to determine whether the neural circuitry involved in face encoding was disrupted in individuals with FXS, and whether brain activity during face encoding was related to levels of social anxiety. A group of 11 individuals with FXS (5 M) and 11 age- and gender-matched control participants underwent fMRI scanning while performing a face encoding task with online eye-tracking. Results indicate that compared to the control group, individuals with FXS exhibited decreased activation of prefrontal regions associated with complex social cognition, including the medial and superior frontal cortex, during successful face encoding. Further, the FXS and control groups showed significantly different relationships between measures of social anxiety (including gaze-fixation) and brain activity during face encoding. These data indicate that social anxiety in FXS may be related to the inability to successfully recruit higher level social cognition regions during the initial phases of memory formation.
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Temperamentally anxious individuals can be identified in childhood and are at risk to develop anxiety and depressive disorders. In addition, these individuals tend to have extreme asymmetric right prefrontal brain activity. Although common and clinically important, little is known about the pathophysiology of anxious temperament. Regardless, indirect evidence from rodent studies and difficult to interpret primate studies is used to support the hypothesis that the amygdala plays a central role. In previous studies using rhesus monkeys, we characterized an anxious temperament endophenotype that is associated with excessive anxiety and fear-related responses and increased electrical activity in right frontal brain regions. To examine the role of the amygdala in mediating this endophenotype and other fearful responses, we prepared monkeys with selective fiber sparing ibotenic acid lesions of the amygdala. Unconditioned trait-like anxiety-fear responses remained intact in monkeys with >95% bilateral amygdala destruction. In addition, the lesions did not affect EEG frontal asymmetry. However, acute unconditioned fear responses, such as those elicited by exposure to a snake and to an unfamiliar threatening conspecific were blunted in monkeys with >70% lesions. These findings demonstrate that the primate amygdala is involved in mediating some acute unconditioned fear responses but challenge the notion that the amygdala is the key structure underlying the dispositional behavioral and physiological characteristics of anxious temperament.
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Mindfulness-based cognitive therapy for children (MBCT-C) is a manualized group psychotherapy for children ages 9–13 years old, which was developed specifically to increase social-emotional resiliency through the enhancement of mindful attention. Program development is described along with results of the initial randomized controlled trial. We tested the hypotheses that children randomized to participate in MBCT-C would show greater reductions in (a) attention problems, (b) anxiety symptoms, and (c) behavior problems than wait-listed age and gender-matched controls. Participants were boys and girls aged 9–13 (N = 25), mostly from low-income, inner-city households. Twenty-one of 25 children were ethnic minorities. A randomized cross-lagged design provided a wait-listed control group, a second trial of MBCT-C, and a 3-month follow-up of children who completed the first trial. Measures included the Child Behavior Checklist, State-Trait Anxiety Inventory for Children, and Multidimensional Anxiety Scale for Children. Participants who completed the program showed fewer attention problems than wait-listed controls and those improvements were maintained at three months following the intervention [F (1, 1, 18) = 5.965, p = .025, Cohen’s d = .42]. A strong relationship was found between attention problems and behavior problems (r = .678, p < .01). Reductions in attention problems accounted for 46% of the variance of changes in behavior problems, although attention changes proved to be a non-significant mediator of behavior problems (p = .053). Significant reductions in anxiety symptoms and behavior problems were found for those children who reported clinically elevated levels of anxiety at pretest (n = 6). Results show that MBCT-C is a promising intervention for attention and behavior problems, and may reduce childhood anxiety symptoms.
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Relationships were investigated between home practice of mindfulness meditation exercises and levels of mindfulness, medical and psychological symptoms, perceived stress, and psychological well-being in a sample of 174 adults in a clinical Mindfulness-Based Stress Reduction (MBSR) program. This is an 8- session group program for individuals dealing with stress-related problems, illness, anxiety, and chronic pain. Participants completed measures of mindfulness, perceived stress, symptoms, and well-being at pre- and post-MBSR, and monitored their home practice time throughout the intervention. Results showed increases in mindfulness and well-being, and decreases in stress and symptoms, from pre- to post-MBSR. Time spent engaging in home practice of formal meditation exercises (body scan, yoga, sitting meditation) was significantly related to extent of improvement in most facets of mindfulness and several measures of symptoms and well-being. Increases in mindfulness were found to mediate the relationships between formal mindfulness practice and improvements in psychological functioning, suggesting that the practice of mindfulness meditation leads to increases in mindfulness, which in turn leads to symptom reduction and improved well-being

Depression has been associated with dysfunctional executive functions and abnormal activity within the anterior cingulate cortex (ACC), a region critically involved in action regulation. Prior research invites the possibility that executive deficits in depression may arise from abnormal responses to negative feedback or errors, but the underlying neural substrates remain unknown. We hypothesized that abnormal reactions to error would be associated with dysfunctional rostral ACC activity, a region previously implicated in error detection and evaluation of the emotional significance of events. To test this hypothesis, subjects with low and high Beck Depression Inventory (BDI) scores performed an Eriksen Flanker task. To assess whether tonic activity within the rostral ACC predicted post-error adjustments, 128-channel resting EEG data were collected before the task and analyzed with low-resolution electromagnetic tomography (LORETA) using a region-of-interest approach. High BDI subjects were uniquely characterized by significantly lower accuracy after incorrect than correct trials. Mirroring the behavioral findings, high BDI subjects had significantly reduced pretask gamma (36.5-44 Hz) current density within the affective (rostral; BA24, BA25, BA32) but not cognitive (dorsal; BA24', BA32') ACC subdivision. For low, but not high, BDI subjects pretask gamma within the affective ACC subdivision predicted post-error adjustments even after controlling for activity within the cognitive ACC subdivision. Abnormal responses to errors may thus arise due to lower activity within regions subserving affective and/or motivational responses to salient cues. Because rostral ACC regions have been implicated in treatment response in depression, our findings provide initial insight into putative mechanisms fostering treatment response.
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Numerous studies demonstrate that the rhesus monkey is an excellent species with which to investigate mechanisms underlying human emotion and psychopathology. To examine the role of the central nucleus of the amygdala (CeA) in mediating the behavioral and physiological responses associated with fear and anxiety, we used rhesus monkeys to assess the effects of excitotoxic lesions of the CeA. Behavioral and physiological responses of nine monkeys with bilateral CeA destruction (ranging from 46 to 98%) were compared with five animals with asymmetric lesions (42-86.5% destruction on the most affected side) and with 16 unoperated controls. Results suggest that similar to rodent species, the primate CeA plays a role in mediating fear- and anxiety-related behavioral and endocrine responses. Compared with controls and the asymmetric-lesion group, bilaterally lesioned monkeys displayed significantly less fear-related behavior when exposed to a snake and less freezing behavior when confronted by a human intruder. In addition, bilaterally lesioned monkeys had decreased levels of CSF corticotrophin-releasing factor (CRF), and both lesioned groups had decreased plasma ACTH concentrations. In contrast to these findings, patterns of asymmetric frontal brain electrical activity, as assessed by regional scalp EEG, did not significantly differ between control and lesioned monkeys. These findings suggest that in primates, the CeA is involved in mediating fear- and anxiety-related behavioral and pituitary-adrenal responses as well as in modulating brain CRF activity.
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BACKGROUND: Excessive behavioral inhibition during childhood marks anxious temperament and is a risk factor for the development of anxiety and affective disorders. Studies in nonhuman primates can provide important information related to the expression of this risk factor, since threat-induced freezing in rhesus monkeys is a trait-like characteristic analogous to human behavioral inhibition. The orbitofrontal cortex (OFC) and amygdala are part of a circuit involved in the processing of emotions and associated physiological responses. Earlier work demonstrated involvement of the primate central nucleus of the amygdala (CeA) in mediating anxious temperament. This study assessed the role of the primate OFC in mediating anxious temperament and its involvement in fear responses. METHODS: Twelve adolescent rhesus monkeys were studied (six lesion and six control monkeys). Lesions were targeted at regions of the OFC that are most interconnected with the amygdala. Behavior and physiological parameters were assessed before and after the lesions. RESULTS: The OFC lesions significantly decreased threat-induced freezing and marginally decreased fearful responses to a snake. The lesions also resulted in a leftward shift in frontal brain electrical activity consistent with a reduction in anxiety. The lesions did not significantly decrease hypothalamic-pituitary-adrenal (HPA) activity or cerebrospinal fluid (CSF) concentrations of corticotrophin-releasing factor (CRF). CONCLUSIONS: These findings demonstrate a role for the OFC in mediating anxious temperament and fear-related responses in adolescent primates. Because of the similarities between rhesus monkey threat-induced freezing and childhood behavioral inhibition, these findings are relevant to understanding mechanisms underlying anxious temperament in humans.
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Our objective was to conduct the first randomized controlled trial of the efficacy of a group mindfulness program aimed at reducing and preventing depression in an adolescent school-based population. For each of 12 pairs of parallel classes with students (age range 13–20) from five schools (N = 408), one class was randomly assigned to the mindfulness condition and one class to the control condition. Students in the mindfulness group completed depression assessments (the Depression Anxiety Stress Scales) prior to and immediately following the intervention and 6 months after the intervention. Control students completed the questionnaire at the same times as those in the mindfulness group. Hierarchical linear modeling showed that the mindfulness intervention showed significantly greater reductions (and greater clinically significant change) in depression compared with the control group at the 6-month follow-up. Cohen's d was medium sized (>.30) for both the pre-to-post and pre-to-follow-up effect for depressive symptoms in the mindfulness condition. The findings suggest that school-based mindfulness programs can help to reduce and prevent depression in adolescents.
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The serotonin transporter (5-HTT) plays a critical role in regulating serotonergic neurotransmission and is implicated in the pathophysiology of anxiety and affective disorders. Positron emission tomography scans using [(11)C]DASB [(11)C]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile] to measure 5-HTT availability (an index of receptor density and binding) were performed in 34 rhesus monkeys in which the relationship between regional brain glucose metabolism and anxious temperament was previously established. 5-HTT availability in the amygdalohippocampal area and bed nucleus of the stria terminalis correlated positively with individual differences in a behavioral and neuroendocrine composite of anxious temperament. 5-HTT availability also correlated positively with stress-induced metabolic activity within these regions. Collectively, these findings suggest that serotonergic modulation of neuronal excitability in the neural circuitry associated with anxiety mediates the developmental risk for affect-related psychopathology.
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<p>Background : Recent research suggests that the Mindfulness-Based Stress Reduction program has positive effects on health, but little is known about the immediate physiological effects of different components of the program. Purpose : To examine the short-term autonomic and cardiovascular effects of one of the techniques employed in mindfulness meditation training, a basic body scan meditation. Methods : In Study 1, 32 healthy young adults (23 women, 9 men) were assigned randomly to either a meditation, progressive muscular relaxation or wait-list control group. Each participated in two laboratory sessions 4 weeks apart in which they practiced their assigned technique. In Study 2, using a within-subjects design, 30 healthy young adults (15 women, 15 men) participated in two laboratory sessions in which they practiced meditation or listened to an audiotape of a popular novel in counterbalanced order. Heart rate, cardiac respiratory sinus arrhythmia (RSA), and blood pressure were measured in both studies. Additional measures derived from impedance cardiography were obtained in Study 2. Results : In both studies, participants displayed significantly greater increases in RSA while meditating than while engaging in other relaxing activities. A significant decrease in cardiac pre-ejection period was observed while participants meditated in Study 2. This suggests that simultaneous increases in cardiac parasympathetic and sympathetic activity may explain the lack of an effect on heart rate. Female participants in Study 2 exhibited a significantly larger decrease in diastolic blood pressure during meditation than the novel, whereas men had greater increases in cardiac output during meditation compared to the novel. Conclusions : The results indicate both similarities and differences in the physiological responses to body scan meditation and other relaxing activities.</p>

OBJECTIVE: Although the efficacy of meditation interventions has been examined among adult samples, meditation treatment effects among youth are relatively unknown. We systematically reviewed empirical studies for the health-related effects of sitting-meditative practices implemented among youth aged 6 to 18 years in school, clinic, and community settings. METHODS: A systematic review of electronic databases (PubMed, Ovid, Web of Science, Cochrane Reviews Database, Google Scholar) was conducted from 1982 to 2008, obtaining a sample of 16 empirical studies related to sitting-meditation interventions among youth. RESULTS: Meditation modalities included mindfulness meditation, transcendental meditation, mindfulness-based stress reduction, and mindfulness-based cognitive therapy. Study samples primarily consisted of youth with preexisting conditions such as high-normal blood pressure, attention-deficit/hyperactivity disorder, and learning disabilities. Studies that examined physiologic outcomes were composed almost entirely of African American/black participants. Median effect sizes were slightly smaller than those obtained from adult samples and ranged from 0.16 to 0.29 for physiologic outcomes and 0.27 to 0.70 for psychosocial/behavioral outcomes. CONCLUSIONS: Sitting meditation seems to be an effective intervention in the treatment of physiologic, psychosocial, and behavioral conditions among youth. Because of current limitations, carefully constructed research is needed to advance our understanding of sitting meditation and its future use as an effective treatment modality among younger populations.

<p>The Buddhist technical term was first translated as ‘mindfulness’ by T.W. Rhys Davids in 1881. Since then various authors, including Rhys Davids, have attempted definitions of what precisely is meant by mindfulness. Initially these were based on readings and interpretations of ancient Buddhist texts. Beginning in the 1950s some definitions of mindfulness became more informed by the actual practice of meditation. In particular, Nyanaponika's definition appears to have had significant influence on the definition of mindfulness adopted by those who developed MBSR and MBCT. Turning to the various aspects of mindfulness brought out in traditional Theravāda definitions, several of those highlighted are not initially apparent in the definitions current in the context of MBSR and MBCT. Moreover, the MBSR and MBCT notion of mindfulness as ‘non-judgmental’ needs careful consideration from a traditional Buddhist perspective. Nevertheless, the difference in emphasis apparent in the theoretical definitions of mindfulness may not be so significant in the actual clinical application of mindfulness techniques.</p>

We used fMRI to examine amygdala activation in response to fearful facial expressions, measured over multiple scanning sessions. 15 human subjects underwent three scanning sessions, at 0, 2 and 8 weeks. During each session, functional brain images centered about the amygdala were acquired continuously while participants were shown alternating blocks of fearful, neutral and happy facial expressions. Intraclass correlation coefficients calculated across the sessions indicated stability of response in left amygdala to fearful faces (as a change from baseline), but considerably less left amygdala stability in responses to neutral expressions and for fear versus neutral contrasts. The results demonstrate that the measurement of fMRI BOLD responses in amygdala to fearful facial expressions might be usefully employed as an index of amygdala reactivity over extended periods. While signal change to fearful facial expressions appears robust, the experimental design employed here has yielded variable responsivity within baseline or comparison conditions. Future studies might manipulate the experimental design to either amplify or attenuate this variability, according to the goals of the research.
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The present study was undertaken to determine whether aversiveness contributes to startle potentiation in anticipation of affective pictures above and beyond the effects of emotional arousal. Further, participants high in trait anxious apprehension, which is characterized by worry about the future, were expected to show especially pronounced anticipatory startle responses. Startle blink reflex was measured during warning stimuli that predicted the valence of ensuing aversive/unpleasant, pleasant, or neutral pictures. Startle magnitude was larger in anticipation of aversive than of pleasant pictures and smallest in anticipation of neutral pictures. Enhanced startle potentiation was not found in anxious apprehension subjects. These data suggest that the aversive nature of stimuli contribute to the potentiation of startle above and beyond the effects of emotional arousal, which may be a universal phenomenon not modulated by individual differences.
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Purpose: To systematically review articles reporting on depression, anxiety, and burnout among U.S. and Canadian medical students. Method: Medline and PubMed were searched to identify peer-reviewed English-language studies published between January 1980 and May 2005 reporting on depression, anxiety, and burnout among U.S. and Canadian medical students. Searches used combinations of the Medical Subject Heading terms medical student and depression, depressive disorder major, depressive disorder, professional burnout, mental health, depersonalization, distress, anxiety, or emotional exhaustion. Reference lists of retrieved articles were inspected to identify relevant additional articles. Demographic information, instruments used, prevalence data on student distress, and statistically significant associations were abstracted. Results: The search identified 40 articles on medical student psychological distress (i.e., depression, anxiety, burnout, and related mental health problems) that met the authors' criteria. No studies of burnout among medical students were identified. The studies suggest a high prevalence of depression and anxiety among medical students, with levels of overall psychological distress consistently higher than in the general population and age-matched peers by the later years of training. Overall, the studies suggest psychological distress may be higher among female students. Limited data were available regarding the causes of student distress and its impact on academic performance, dropout rates, and professional development. Conclusions: Medical school is a time of significant psychological distress for physicians-in-training. Currently available information is insufficient to draw firm conclusions on the causes and consequences of student distress. Large, prospective, multicenter studies are needed to identify personal and training-related features that influence depression, anxiety, and burnout among students and explore relationships between distress and competency.

<p>Few counseling programs directly address the importance of self-care in reducing stress and burnout in their curricula. A course entitled Mind/Body Medicine and the Art of Self-Care was created to address personal and professional growth opportunities through self-care and mindfulness practices (meditation, yoga, qigong, and conscious relaxation exercises). Three methods of evaluating this 15-week 3-credit mindfulness-based stress reduction (MBSR) course for counseling students indicated positive changes for students in learning how to manage stress and improve counseling practice. Students reported positive physical, emotional, mental, spiritual, and interpersonal changes and substantial effects on their counseling skills and therapeutic relationships. Information from a focus group, qualitative reports, and quantitative course evaluations were triangulated; all data signified positive student responses to the course, method of teaching, and course instructor. Most students reported intentions of integrating mindfulness practices into their future profession.</p>

<p>Preparation for the role of therapist can occur on both professional and personal levels. Research has found that therapists are at risk for occupationally related psychological problems. It follows that self-care may be a useful complement to the professional training of future therapists. The present study examined the effects of one approach to self-care, Mindfulness-Based Stress Reduction (MBSR), for therapists in training. Using a prospective, cohort-controlled design, the study found participants in the MBSR program reported significant declines in stress, negative affect, rumination, state and trait anxiety, and significant increases in positive affect and self-compassion. Further, MBSR participation was associated with increases in mindfulness, and this enhancement was related to several of the beneficial effects of MBSR participation. Discussion highlights the potential for future research addressing the mental health needs of therapists and therapist trainees.</p>

Several randomised controlled trials suggest that mindfulness-based approaches are helpful in preventing depressive relapse and recurrence, and the UK Government’s National Institute for Health and Clinical Excellence has recommended these interventions for use in the National Health Service. There are good grounds to suggest that mindfulness-based approaches are also helpful with anxiety disorders and a range of chronic physical health problems, and there is much clinical and research interest in applying mindfulness approaches to other populations and problems such as people with personality disorders, substance abuse, and eating disorders. We review the UK context for developments in mindfulness-based approaches and set out criteria for mindfulness teacher competence and training steps, as well as some of the challenges and future directions that can be anticipated in ensuring that evidence-based mindfulness approaches are available in health care and other settings.
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<p>This study is an open clinical trial that examined the feasibility and acceptability of a mindfulness training program for anxious children. We based this pilot initiative on a cognitively oriented model, which suggests that, since impaired attention is a core symptom of anxiety, enhancing self-management of attention should effect reductions in anxiety. Mindfulness practices are essentially attention enhancing techniques that have shown promise as clinical treatments for adult anxiety and depression (Baer, 2003). However, little research explores the potential benefits of mindfulness to treat anxious children. The present study provided preliminary support for our model of treating childhood anxiety with mindfulness. A 6-week trial was conducted with five anxious children aged 7 to 8 years old. The results of this study suggest that mindfulness can be taught to children and holds promise as an intervention for anxiety symptoms. Results suggest that clinical improvements may be related to initial levels of attention.</p>

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